Cytokine-induced killer cells mediated pathways in the treatment of colorectal cancer

Fayyaz, Farimah; Yazdanpanah, Niloufar; Rezaei, Nima

doi:10.1186/s12964-022-00836-0

Cited by 12 publications

(4 citation statements)

References 69 publications

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“… 20 , 21 In contrast, previous studies have attempted to investigate the impact of combining chemotherapy with CIK/DC-CIK cell immunotherapy in patients with mCRC, and the findings indicated that the addition of CIK/DC-CIK cells to chemotherapy significantly improved clinical outcomes compared with chemotherapy alone. 13 , 22 Our previous phase II study also found that CIK cell therapy combined with 5-fluorouridine, leucovorin and oxaliplatin (FOLFOX4) chemotherapy significantly prolonged OS when compared to the use of chemotherapy alone as an initial treatment for patients with mCRC; while the PFS was not significantly improved. 17 The current study demonstrated that PD1-T cells combined with XELOX plus bevacizumab exhibited superior efficacy in terms of PFS and OS compared to XELOX plus bevacizumab alone.…”

Section: Discussionmentioning

confidence: 98%

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial

Pan,

Zhao,

Liu

et al. 2024

Sig Transduct Target Ther

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Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6–18.0) for the immunotherapy group compared with 9.9 months (8.0–11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40–0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3–32.8) for the control group (HR, 0.57 [95% CI, 0.33–0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

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Section: Discussionmentioning

confidence: 98%

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial

Pan,

Zhao,

Liu

et al. 2024

Sig Transduct Target Ther

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“…Other immune cells-based therapies have been explored due to their distinct advantages, including NK cells, 176 gamma delta T cells (γδT), 177 CD3 activated killer cells, 178 cytokine-induced killer cells (CIK), 179 dendritic cellcytokine induced killer cells (DC-CIK) 180 and lymphokineactivated killer cells. 181,182 These cell-based therapies have shown continuous progress in efficacy, specificity and reduction of side effects.…”

Section: Other Immune Cells-based Therapiesmentioning

confidence: 99%

Tumour organoids and assembloids: Patient‐derived cancer avatars for immunotherapy

Mei,

Liu,

Tian

et al. 2024

Clinical & Translational Med

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BackgroundOrganoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch‐to‐batch variations, lack of the native microenvironment and clinical applicability.Main bodyThe concept of organoids has derived patient‐derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, ‘tumour assembloids’ inspired by cell‐coculture technology have attracted attention to complement the current PDTO technology. High‐quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour‐infiltrating lymphocyte, T cell receptor‐engineered T cell and chimeric antigen receptor‐T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank.ConclusionFundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre‐clinical immunotherapy screening using PDTOs will be beneficial to cancer patients.Key Points The current PDTO models have not yet constructed key cellular and non‐cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.

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“…These individual nucleated cells are obtained through ex vivo cultivation (11–15 days), where they undergo stimulation with various cytokines, such as anti‐CD3 monoclonal antibodies, IL‐2, and IFN‐γ, to induce their cytotoxic activity. [ 136 ] This promising immune effector cell population combines both, innate and adoptive immune responses, possessing potent antitumor activity similar to T lymphocytes and the MHC‐unrestricted tumor‐killing advantages of NK cells. [ 137 ] The immunotherapy based on CAR‐CIK has been validated in several studies.…”

Section: Off‐the‐shelf Car‐based Agentsmentioning

confidence: 99%

Advances in CAR‐Engineered Immune Cell Generation: Engineering Approaches and Sourcing Strategies

Chen,

Hu,

Mei

2023

Advanced Science

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Chimeric antigen receptor T‐cell (CAR‐T) therapy has emerged as a highly efficacious treatment modality for refractory and relapsed hematopoietic malignancies in recent years. Furthermore, CAR technologies for cancer immunotherapy have expanded from CAR‐T to CAR‐natural killer cell (CAR‐NK), CAR‐cytokine‐induced killer cell (CAR‐CIK), and CAR‐macrophage (CAR‐MΦ) therapy. Nevertheless, the high cost and complex manufacturing processes of ex vivo generation of autologous CAR products have hampered broader application. There is an urgent need to develop an efficient and economical paradigm shift for exploring new sourcing strategies and engineering approaches toward generating CAR‐engineered immune cells to benefit cancer patients. Currently, researchers are actively investigating various strategies to optimize the preparation and sourcing of these potent immunotherapeutic agents. In this work, the latest research progress is summarized. Perspectives on the future of CAR‐engineered immune cell manufacturing are provided, and the engineering approaches, and diverse sources used for their development are focused upon.

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Cytokine-induced killer cells mediated pathways in the treatment of colorectal cancer

Cited by 12 publications

References 69 publications

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial

Tumour organoids and assembloids: Patient‐derived cancer avatars for immunotherapy

Advances in CAR‐Engineered Immune Cell Generation: Engineering Approaches and Sourcing Strategies

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